The Luigi Sacco Hospital VAS-COG stroke care pathway: A five-year experience.

Background: Psycho-cognitive consequences are a frequent cause of disability in stroke survivors but are often underdiagnosed also because of lack of services dedicated to these aspects. We started assessing systematically cognitive and behavioral functions in acute stroke patients and to follow them up. Here, we report a retrospective analysis of the organization of the Sacco VAS-COG stroke care pathway and the refinements implemented during 5 years of activity. Methods: The protocol includes baseline collection of clinical history, general and neurologic examinations, functional, neuropsychological, and neuroimaging assessment. At follow-up, a diagnosis of cognitive decline was made based on best clinical judgment in the first period (January 2018 to May 2019, namely VAS-COG protocol 1.0) and then based on an extensive neuropsychological battery (May 2019 to January 2023, namely VASCOG protocol 2.0); psychiatric and behavioral disturbances are investigated through suitable scales. Results: From January 2018 to December 2022, 834 patients (mean age 76±13.6 years; 46.6 % females) with acute cerebrovascular events were admitted to the stroke unit, mostly (80 %) for ischemic strokes. Pre-event cognitive impairment was not assessable in 78 patients (9.3 %) because no reliable informant was present and was reported in 327/756 (43 %) patients. During follow-up, post-stroke cognitive impairment was detected in 124/217 (57.1 %) patients in VAS-COG protocol 1.0 and in 137/201(68.2 %) patients in VAS-COG protocol 2.0, while 95/218 (43.2 %) patients were found to be depressed and patients presented on average 2.5 neuropsychiatric symptoms on Neuropsychiatric Inventory-questionnaire. Conclusions: The VAS-COG stroke care pathway represents a model for patients and for their families.

Child abuse and neglect: oral and dental signs and the role of the dentist.

Historically, the law, dental and forensic literature has included numerous articles concerning abused children. The orofacial structures are injured frequently in the maltreated child. Injuries of the neck, head, face, and oral cavity represent the most affected areas of the victim's body that routinely sustain physical trauma in child maltreatment cases. This literature review aimed to report the state of art of child abuse from the point of view of the dentist with focus on studies in dental aspects of child abuse and neglect of the last ten years. Considering the time slot, 20 papers were included with the following inclusion criteria: papers published in English, all keywords included in the title, articles available on PubMed. Many of the injuries are within the scope of dentistry or easily observed by the dental professional during routine dental treatment, and it is essential that the dentist recognizes them. Concerning neglect, it is appropriate to make a distinction between deliberate parental behavior that has the consequence of unavoidable and voluntary neglect towards their children and those conditions of involuntary carelessness determined by socio-economic and cultural factors such as family isolation, lack of finances, parental ignorance, or lack of perceived value of oral health. Therefore, it is relevant that the dentist pays attention to the cases to report and those that only need help.

A new paradigm of hospital care for SARS-COV-2 patients in the post-emergency phase in Italy.

Abstract: In Italy, at the beginning of the SARS-CoV-2 pandemic, the main organizational model of hospital care was represented by the physical or functional division of hospitals and wards into COVID and non-COVID areas, in order to separate SARS-CoV-2-infected patients from the others. Now that the emergency phase has reached its long-awaited end, it is necessary to develop a new hospital care paradigm that may deal with SARS-CoV-2-positive patients discriminating between those who are hospitalized because of COVID-19 and those who are diagnosed with SARS-CoV-2 infection immediately before or after the first access to healthcare facilities.

Reverse engineering in forensic investigations: a new approach to bite mark analysis.

The study of bite marks provides crucial elements that contribute towards identifying the biter. In many cases, it assumes importance when bite marks are detected on the body of a victim of violence, but it could also be relevant when the bite marks are seen on food substances at the crime scene. In both circumstances, comparing the bite marks with a suspect's dentition can be decisive in confirming or excluding the culpability. In this case report, a bun (bread roll) with the sign of a bite was found at the crime scene. We report a pilot study using 3D reproduction of the bite mark on the bun and dental models of the alleged biter and the victim. A reverse engineering process was used to obtain digital 3D models of the bitten bun and the dental models by taking numerous photographs and stitching them together using a software called Metashape by Agisoft. The last step was to compare the bitemark to the two dental models, evaluating the spatial distance, the degree of overlap, and the degree of interpenetration. The results confirmed the usefulness of reverse engineering in forensic investigations showing the compatibility between the victim's teeth and the bite mark on the bun.

Facial approximation for identification purposes: soft tissue thickness in a Caucasian population. Sex and age-related variations.

The aim of this study was to collect soft tissue thickness (STT) values of an Italian population from 12 bone landmarks, to improve the facial approximation process for identification purposes. 100 Italian adults (50 males and 50 females), who had undergone head CT for clinical purposes, were analysed in order to expand the database of the Italian population. Average values, standard deviation and range were collected according to gender and age and the obtained values were statistically analysed in order to evaluate any possible significant difference. Only one landmark was statistically significant associated with sex, females showed significantly higher values for para-zygomaxillary. Two landmarks were statistically significant associated with age, upper incisor and pogonion. The obtained results were compared with the existing literature. Such information can be useful in the forensic craniofacial reconstruction process and can facilitate choosing the most suitable STT values according to osteological analysis of the human remains.

Drugs and liver injury: a not to be overlooked binomial in COVID-19.

SARS-CoV-2 infection (COVID-19) results predominantly in pulmonary involvement but a direct, virus-induced liver damage may also occur, whose mechanisms are being actively investigated. Accordingly, it appears of utmost importance to monitor liver function and carefully evaluate hepatic safety of the various drugs administered during COVID-19. In this respect, many drugs, biological agents and novel molecules, whose efficacy in COVID-19 is under scrutiny, have also been shown to potentially cause or worsen liver damage. In this article, we review safety data of established as well as promising agents for COVID-19.

Probabilistic tsunami forecasting for early warning.

Tsunami warning centres face the challenging task of rapidly forecasting tsunami threat immediately after an earthquake, when there is high uncertainty due to data deficiency. Here we introduce Probabilistic Tsunami Forecasting (PTF) for tsunami early warning. PTF explicitly treats data- and forecast-uncertainties, enabling alert level definitions according to any predefined level of conservatism, which is connected to the average balance of missed-vs-false-alarms. Impact forecasts and resulting recommendations become progressively less uncertain as new data become available. Here we report an implementation for near-source early warning and test it systematically by hindcasting the great 2010 M8.8 Maule (Chile) and the well-studied 2003 M6.8 Zemmouri-Boumerdes (Algeria) tsunamis, as well as all the Mediterranean earthquakes that triggered alert messages at the Italian Tsunami Warning Centre since its inception in 2015, demonstrating forecasting accuracy over a wide range of magnitudes and earthquake types.

Personal identification through digital photo superimposition of dental profile: a pilot study.

The usefulness of teeth for personal identification lies mainly in their vast individual variability, making them virtually unique for every subject. Odontological identification represents a reliable and important complement to forensic inquiries, in particular in the event of unidentifiable human remains. However, this technique is based on the availability of ante-mortem records containing significant evidence. In the absence of dental records, the only available ante-mortem elements are often photographs. In the present study, dental profile photographs of selected smiling subjects were compared to the relevant plaster study models through digital image analysis. In order to ascertain the reliability of the technique, the comparison was carried out both in a homologous and heterologous manner with the Facecomp software. The results confirm the ability of Facecomp software to identify even the smallest variations in dental elements to reach a positive identification. The method is useful in forensic practice since a forensic inquiry may obtain plaster models from cadavers for comparison with photographs of missing people's anterior teeth.

Dissection of DLBCL microenvironment provides a gene expression-based predictor of survival applicable to formalin-fixed paraffin-embedded tissue.

Background: Gene expression profiling (GEP) studies recognized a prognostic role for tumor microenvironment (TME) in diffuse large B-cell lymphoma (DLBCL), but the routinely adoption of prognostic stromal signatures remains limited. Patients and methods: Here, we applied the computational method CIBERSORT to generate a 1028-gene matrix incorporating signatures of 17 immune and stromal cytotypes. Then, we carried out a deconvolution on publicly available GEP data of 482 untreated DLBCLs to reveal associations between clinical outcomes and proportions of putative tumor-infiltrating cell types. Forty-five genes related to peculiar prognostic cytotypes were selected and their expression digitally quantified by NanoString technology on a validation set of 175 formalin-fixed, paraffin-embedded DLBCLs from two randomized trials. Data from an unsupervised clustering analysis were used to build a model of clustering assignment, whose prognostic value was also assessed on an independent cohort of 40 cases. All tissue samples consisted of pretreatment biopsies of advanced-stage DLBCLs treated by comparable R-CHOP/R-CHOP-like regimens. Results: In silico analysis demonstrated that higher proportion of myofibroblasts (MFs), dendritic cells, and CD4+ T cells correlated with better outcomes and the expression of genes in our panel is associated with a risk of overall and progression-free survival. In a multivariate Cox model, the microenvironment genes retained high prognostic performance independently of the cell-of-origin (COO), and integration of the two prognosticators (COO + TME) improved survival prediction in both validation set and independent cohort. Moreover, the major contribution of MF-related genes to the panel and Gene Set Enrichment Analysis suggested a strong influence of extracellular matrix determinants in DLBCL biology. Conclusions: Our study identified new prognostic categories of DLBCL, providing an easy-to-apply gene panel that powerfully predicts patients' survival. Moreover, owing to its relationship with specific stromal and immune components, the panel may acquire a predictive relevance in clinical trials exploring new drugs with known impact on TME.

[Pelvic lymphadenectomy as an alternative to adjuvant radiotherapy in early stage endometrial cancer at high risk of recurrent lymphatic metastases (stage I)]. / Linfoadenectomia pelvica come alternativa alla radioterapia adiuvante nel carcinoma endometriale ad alto rischio di metastasi linfonodali in fase precoce (stadio I).

AIM: The aim of this study was to evaluate if the surgical approach without pelvic lymphadenectomy and with adjuvant radiotherapy in the patients suffering from endometrioid adenocarcinoma type at high risk (of lymphatic metastasis) in early stage can be substituted by only surgery with pelvic lymphadenectomy (with or without para-aortic lymphadenectomy). METHODS: A retrospective study was carried out on 56 patients who underwent surgery with eventual adjuvant radiotherapy and were attended during the follow-up in the Operative Unit of Gynecology and Obstetrics from 1997 to 2004. The patients were divided into two groups: the low risk group and the high risk group. The cancer grading (G) was defined before the surgery with an hystological exam on endometrial biopsies. The follow-up had a medium duration of 30 months (range: 9-44 months) and consisted of the evaluation of: cancer related survival (CRS); recurrence free survival (RFS). Both were evaluated according to age, risk type, and therapy adopted. RESULTS: Four patients (7.1%) showed relapse during the period of study in a medium time of 24 months (range: 12-36): 2 of these patients (C and D cases; 36%) had a relapse both locally (pelvic wall) and distantly; the other two (A and B cases; 36%) had only a distant relapse. None of the patients at the stage IA had a relapse, but it occurred in the 8.7% of the cases (N.=2) IB and in the 10.5 % of the patients IC (N.=2). One patient of the low risk group (3.8%) (case A) had a distant relapse (lungs) 12 months after the surgery and died 6 months after the appearance of the relapse without any additional treatment, because of age and of concomitant pathologies which suggested another illness. Three patients of the high risk group (10%) had a local and /or distant relapse (one only distant, two both distant and local). One of them with distant relapse (36 months after the primary treatment) (case B) is still alive, even though she has got a controlled cancer, 8 months after the rescue treatment (chemotherapy), whereas two of them died in a medium time of 14 months (range 13-15 months) from the rescue treatment (C and D cases). One of the three patients of the high risk group underwent the standard surgical treatment with lympho-adenectomy (case B) whereas the other two underwent the standard surgical treatment with aiding radiotherapy (C and D cases). The CRS and the RFS were 96.2% and 96.2% in the low risk group, 93.3% and 90% in the high risk group, respectively. CONCLUSIONS: The standard surgery offers a good prognosis to the low risk group patients. To the high risk group the CRS and the RFS were better with standard surgery with lymphadenectomy than with standard surgery with adjuvant radiotherapy. The degree of differentiation of the cancer is the most important prognostic factor in relation to the survival free from relapse (RFS).

A short low-level exposure to metavanadate during a cell cycle-specific interval of time is sufficient to permanently derange the differentiative properties of Mel cells.

Mouse erythroleukemia (Mel) cells have a cell cycle-dependent high sensitivity to chemical and physical mutagens. This report shows that a 5 h exposure to 0.1 or 0.01 microg/ml metavanadate during the initial period of erythroid differentiation induction was sufficient to permanently damage the ability of treated Mel cells and their progeny to undergo erythroid differentiation, without affecting cell viability and proliferation. Conversely, a 5 h pulse of metavanadate at 1 or 10 microg/ml inhibited both differentiation and cell proliferation. The cell cycle-dependent period of mutagenesis was essential for fixation of damage in the cell genome and the progeny of the cells treated with 0.1 or 0.01 microg/ml metavanadate stably inherited an impaired capacity to differentiate. The efficiency of the DNA repair synthesis machinery during the specific period of exposure of Mel cells seemed directly involved in damage fixation. In fact, the mutagenic effects of a 0.1 microg/ml metavanadate pulse was further increased in the presence of 1 mM hydroxyurea, an inhibitor of DNA repair synthesis. In contrast, 5 microg/ml vanillin, an antimutagenic agent that stimulates repair, completely restored the capacity of progeny of cells treated with 0.1 microg/ml metavanadate to complete differentiation. Determination of [(3)H]deoxythymidine in acid-insoluble DNA indicated that incorporation was stimulated by metavanadate alone and was further increased by metavanadate plus vanillin; conversely, incorporation of thymidine was reduced in the presence of hydroxyurea. The capacity of metavanadate to permanently damage Mel cell erythroid differentiation appeared to depend on the cell cycle-related efficiency of the DNA repair systems, activated to correct the induced alteration, rather than on a specific concentration.

Pleural effusions: patterns on ventilation-perfusion lung scans.

Perfusion and ventilation abnormalities created by pleural effusions can interfere with the interpretation of the lung scan. This retrospective study identified and evaluated the specificity of scintigraphic patterns for pleural effusion. Ninety-two ventilation-perfusion lung scans were analyzed for the following signs of pleural effusion: presence of fissures, straightened or concave lung borders, costophrenic angle blunting, and attenuation of lung activity by interposed fluid. The findings later were correlated with chest radiographs. Of 25 pleural effusions detected by chest radiography, scintigraphy predicted 14 (specificity, 86%). In all of these cases, there was agreement with the chest radiograph (specificity, 100%). The fissure sign and the straight-concave border sign were equally reliable for the prediction of pleural fluid. Costophrenic angle blunting was never seen as the sole indicator of pleural fluid, and attenuation was seen alone in only one case. Another finding observed during this evaluation was absent ventilation at the lung base with preserved perfusion. Scintigraphic patterns may not be reliable in obstructive lung disorders and diseases with altered lung compliance. The recognition of scintigraphic patterns of pleural effusions on ventilation-perfusion scans can improve the clinical value of lung scintigraphy by reducing the number of indeterminate readings.

Two periods of sensitivity to mutagens in induced Mel cells with different outcomes.

Mouse erythroleukemia (Mel) cells are particularly sensitive to mutagenic agents between 18 and 24 h from the start of induction (Foresti, M.L. Gaudio, G. Geraci and P. Manduca (1986) Inhibition of dimethyl sulfoxide induced erythropoietic differentiation of murine erythroleukemia cells in culture. Cancer Res., 46, 6260-6263). We show here the occurrence of another period of sensitivity during the initial 5 h after the addition of the inducer dimethyl sulfoxide (DMSO) to the culture medium. The sensitivity to the mutagenic action of a sublethal 3-s pulse of UV light (13.5 J/m2) was monitored on the progeny of the irradiated cells at day 5 after the start of induction. The effects were analysed on functions strictly linked to the final expression of the differentiated phenotype: hemoglobin concentration, percent cells producing hemoglobin (%B+), activity of delta-amino levulinic acid dehydrase (ALA-DH) and presence of globins. Each function appeared differently and selectively affected in the progeny of the cells depending on the exact time of irradiation during the period of sensitivity Specifically, cells irradiated at hour 3 after induction show both hemoglobin concentration and ALA-DH activity values increased by a factor 3 over controls. Cells irradiated at hour 5 show an almost complete halt in cell induction and the other tested functions show minimal values. Cells are nearly insensitive to irradiation at later times, until hour 20, after which a second period of sensitivity with peak value at hour 22 occurs at which time hemoglobin concentration in the progeny of irradiated cells is increased by a factor 3 over controls, ALA-DH activity is increased by a factor 15 while percent B+ value is at its minimum. The differential effects of UV irradiation on Mel cell functions in the first and in the second period of sensitivity to mutagens confirm the hypothesis that the consequences of a mutational event are strictly dependent on the functional state of the cell. The 1-5 h period of sensitivity in which Mel cells fix the effects of the mutagen in their genome corresponds to increased thymidine incorporation not correlated with cell duplication.